BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine
BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine
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DOI：
10.3390/cancers11070940
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发表时间：
2019-06-26
期刊：
影响因子：
5.2
通讯作者：
Vales-Gomez, Mar
中科院分区：
文献类型：
--
作者：
Ashiru, Omodele;Esteso, Gloria;Vales-Gomez, Mar
背景：膀胱内滴注卡介苗（BCG）是一种牛分枝杆菌减毒菌株，是治疗高级别非肌层浸润性膀胱癌（NMIBC）的有效疗法，它能激发局部免疫反应，使 70% 的患者在三年后不再复发。由于无反应患者通常预后不良，因此早期识别治疗失败至关重要。我们假设，如果膀胱中发生有效的免疫反应，可溶性因子将在卡介苗滴注后许多天释放到尿液中。方法：在三年多的 NMIBC 患者队列中，对每次 BCG 滴注后 7 天释放到尿液中的大量细胞因子和趋化因子进行了筛查。结果：尿细胞因子、趋化因子和肌酐浓度的测定表明，在接受卡介苗治疗的患者的六周诱导周期中，CD14+细胞释放到尿液中的C-X-C基序趋化因子10（CXCL10）也称为干扰素诱导蛋白10（IP10）的浓度不断增加。在体外，在 T 细胞和自然杀伤 (NK) 细胞中 BCG 介导的 CXCR3 上调后，CXCL10 促进了效应免疫细胞的募集。结论：接触分枝杆菌1周后检测到的高浓度趋化因子提示CXCL10轴可能与免疫抗肿瘤反应的强度有关。
Background: Intra-vesical instillation of Bacille Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14(+) cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.